DESCRIPTION (Adapted from the Investigator's Specific Aims): The overall goals of this project are to use genetic strategies to study the role of leukocyte and endothelial cell adhesion molecules in normal biology and in disease processes. Five Specific Aims are proposed: (1) Develop mutations in all three mouse selectin genes. (2) Perform phenotypic evaluation of knockout mice, including routine pathology, leukocyte counts, peritonitis, pneumonia, delayed type hypersensitivity reactions, and intravital microscopy. (3) Investigate the pathogenesis of psoriasis-like skin disease in CD18 deficient mice, specifically searching for a modifier gene or genes using a genomic-wide linkage strategy. (4) Develop cell-specific and inducible mutations using the loxP/Cre recombinase system, including an endothelial cell-specific mutation for VCAM-1 and an inducible mutations for ICAM-1. (5) Evaluate the role of adhesion molecules in the pathogenesis of atherosclerosis using apolipoprotein E-deficient mice.